The biochemistry of human neutrophil (PMN) microtubule metabolism was studied by monitoring the specific stimulation of the post-translational incorporation of tyrosine into tubulin Alpha-chains by the chemoattractant fmet-leu-phe. The data indicate fmet-leu-phe stimulates tubulin tyrosinolation in normal PMN. Studies in PMN from patients with the Chediak-Higashi syndrome and with chronic granulomatous disease indicated a greatly exaggerated response in the former and inhibited response in the latter. Based on studies of the oxidative state of the patients' cells and studies using oxidizing and reducing agents it is concluded that there is a close association between cellular redox state and tubulin tyrosinolation. In related studies the plant alkaloid taxol was shown to inhibit neutrophil spreading, chemotaxis and bacterial activity without inhibiting expression of fmet-leu-phe, C3b or Fc receptors. Taxol promoted and stabilized assembled microtubules and caused microtubule bundle formation as well as inhibited tubulin tyrosinolation. The data provide new insights into the relationship between microtubule metabolism and neutrophil function.